Antibacterial autophagy occurs at PtdIns(3)P-enriched domains of the endoplasmic reticulum and requires Rab1 GTPase
Antibacterial autophagy occurs at PtdIns(3)P-enriched domains of the endoplasmic reticulum and requires Rab1 GTPase
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DOI：
10.4161/auto.7.1.13840
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发表时间：
2011-01-01
期刊：
影响因子：
13.3
通讯作者：
Brumell, John H.
中科院分区：
文献类型：
--
作者：
Huang, Ju;Birmingham, Cheryl L.;Brumell, John H.
自噬介导真核细胞胞质组分的降解，在免疫中起着关键作用。自噬体的形成机制尚不清楚。在这里，我们研究了抗菌自噬的两个潜在的膜来源：ER和线粒体。DFCP 1是一种被称为“omegasomes”的专门ER结构域的标记物，通过其PtdIns（3）P和ER结合结构域与含沙门氏菌的自噬体相关，而线粒体标记物（细胞色素b5-GFP）则没有。Rab 1也定位于自噬体，其活性是自噬体形成、蛋白质聚集体和过氧化物酶体的清除以及沙门氏菌自噬所必需的。Rab 1的过表达增强抗菌自噬。Rab 1在抗菌性自噬中的作用与其在内质网-高尔基体转运中的作用无关。我们的数据表明，抗菌自噬发生在omegasomes，并揭示Rab 1 GTdR在哺乳动物自噬中起着至关重要的作用。
Autophagy mediates the degradation of cytoplasmic components in eukaryotic cells and plays a key role in immunity. The mechanism of autophagosome formation is not clear. Here we examined two potential membrane sources for antibacterial autophagy: the ER and mitochondria. DFCP1, a marker of specialized ER domains known as 'omegasomes,' associated with Salmonella-containing autophagosomes via its PtdIns(3)P and ER-binding domains, while a mitochondrial marker (cytochrome b5-GFP) did not. Rab1 also localized to autophagosomes, and its activity was required for autophagosome formation, clearance of protein aggregates and peroxisomes, and autophagy of Salmonella. Overexpression of Rab1 enhanced antibacterial autophagy. The role of Rab1 in antibacterial autophagy was independent of its role in ER-to-Golgi transport. Our data suggest that antibacterial autophagy occurs at omegasomes and reveal that the Rab1 GTPase plays a crucial role in mammalian autophagy.